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学科主题: 临床医学
题名:
CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site
作者: Zhuo, De-Xiang1,4; Zhang, Xiao-Wei1; Jin, Bo1; Zhang, Zheng2,3; Xie, Bu-Shan1; Wu, Cheng-Lin1; Gong, Kan2,3; Mao, Ze-Bin1
刊名: PLOS ONE
发表日期: 2013-06-17
DOI: 10.1371/journal.pone.0065679
卷: 8, 期:6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: KINASE-B ; 3-KINASE PATHWAY ; FGFR3 MUTATIONS ; GENE-MUTATIONS ; ACTIVATION ; CARCINOMA ; PHOSPHORYLATION ; IDENTIFICATION ; PTEN/MMAC1 ; PHLPP
英文摘要:

Akt/protein kinase B is a pivotal component downstream of phosphatidylinositol 3-kinase (PI3K) pathway, whose activity regulates the balance between cell survival and apoptosis. Phosphorylation of Akt occurs at two key sites either at Thr308 site in the activation loop or at Ser473 site in the hydrophobic motif. The phosphorylated form of Akt (pAkt) is activated to promote cell survival. The mechanisms of pAkt dephosphorylation and how the signal transduction of Akt pathway is terminated are still largely unknown. In this study, we identified a novel protein phosphatase CSTP1(complete s transactivated protein 1), which interacts and dephosphorylates Akt specifically at Ser473 site in vivo and in vitro, blocks cell cycle progression and promotes cell apoptosis. The effects of CSTP1 on cell survival and cell cycle were abrogated by depletion of phosphatase domain of CSTP1 or by expression of a constitutively active form of Akt (S473D), suggesting Ser473 site of Akt as a primary cellular target of CSTP1. Expression profile analysis showed that CSTP1 expression is selectively down-regulated in non-invasive bladder cancer tissues and over-expression of CSTP1 suppressed the size of tumors in nude mice. Kaplan-Meier curves revealed that decreased expression of CSTP1 implicated significantly reduced recurrence-free survival in patients suffered from non-invasive bladder cancers.

语种: 英语
所属项目编号: 81272827 ; 30971627
项目资助者: National Science Foundation of China
WOS记录号: WOS:000321397800014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56435
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China
2.Peking Univ, Inst Urol, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China
4.Fujian Med Univ, Hosp Sanming 1, Dept Lab Med, Sanming, Fujian, Peoples R China

Recommended Citation:
Zhuo, De-Xiang,Zhang, Xiao-Wei,Jin, Bo,et al. CSTP1, a Novel Protein Phosphatase, Blocks Cell Cycle, Promotes Cell Apoptosis, and Suppresses Tumor Growth of Bladder Cancer by Directly Dephosphorylating Akt at Ser473 Site[J]. PLOS ONE,2013,8(6).
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